CAR T Cell Immunotherapy in Human and Veterinary Oncology

Changing the Odds Against Hematological Malignancies

Jonathan P. Mochel, Stephen C Ekker, Chad M. Johannes, Albert E. Jergens, Karin Allenspach, Agnes Bourgois-Mochel, Michael Knouse, Sebastien Benzekry, Wesley Wierson, Amy K. LeBlanc, Saad Kenderian

Research output: Contribution to journalComment/debate

Abstract

The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T cells for targeted cancer therapy. CAR T cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T cell therapies were approved by the US Food and Drug Administration: one for the treatment of pediatric acute lymphoblastic leukemia (ALL) and the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20–100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin’s lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This commentary summarizes the current state of knowledge on CAR T cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.

Original languageEnglish (US)
Article number50
JournalAAPS Journal
Volume21
Issue number3
DOIs
StatePublished - May 1 2019

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Hematologic Neoplasms
T-Cell Antigen Receptor
Antigen Receptors
Immunotherapy
Canidae
Cell- and Tissue-Based Therapy
Therapeutics
Neoplasms
Adoptive Transfer
B-Cell Lymphoma
United States Food and Drug Administration
Combination Drug Therapy
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Non-Hodgkin's Lymphoma
Transfection
Lymphoma
Bone Marrow
Medicine
Dogs
Pediatrics

Keywords

  • CAR T cell
  • lymphoma
  • ommuno-oncology
  • One Health

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

CAR T Cell Immunotherapy in Human and Veterinary Oncology : Changing the Odds Against Hematological Malignancies. / Mochel, Jonathan P.; Ekker, Stephen C; Johannes, Chad M.; Jergens, Albert E.; Allenspach, Karin; Bourgois-Mochel, Agnes; Knouse, Michael; Benzekry, Sebastien; Wierson, Wesley; LeBlanc, Amy K.; Kenderian, Saad.

In: AAPS Journal, Vol. 21, No. 3, 50, 01.05.2019.

Research output: Contribution to journalComment/debate

Mochel, JP, Ekker, SC, Johannes, CM, Jergens, AE, Allenspach, K, Bourgois-Mochel, A, Knouse, M, Benzekry, S, Wierson, W, LeBlanc, AK & Kenderian, S 2019, 'CAR T Cell Immunotherapy in Human and Veterinary Oncology: Changing the Odds Against Hematological Malignancies', AAPS Journal, vol. 21, no. 3, 50. https://doi.org/10.1208/s12248-019-0322-1
Mochel, Jonathan P. ; Ekker, Stephen C ; Johannes, Chad M. ; Jergens, Albert E. ; Allenspach, Karin ; Bourgois-Mochel, Agnes ; Knouse, Michael ; Benzekry, Sebastien ; Wierson, Wesley ; LeBlanc, Amy K. ; Kenderian, Saad. / CAR T Cell Immunotherapy in Human and Veterinary Oncology : Changing the Odds Against Hematological Malignancies. In: AAPS Journal. 2019 ; Vol. 21, No. 3.
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